This report describes spinocerebellar ataxia, autosomal recessive 32 (SCAR32). The human gene implicated in this disease is PRDX3, which encodes a mitochondrial protein with antioxidant function that plays a role in cell protection against oxidative stress. There is a single high-scoring ortholog in Drosophila, Dmel\Prx3; there are multiple less closely related genes in both species. A limited number of genetic reagents have been generated for Dmel\Prx3, including overexpression and RNAi targeting constructs.
A UAS construct of a wild-type Hsap\PRDX3 gene has been introduced into flies and has been used in investigations of interactions with Hsap\LRRK2, the human gene implicated in Parkinson disease 8 (see FBhh0000011). It has not been used in the context of this disease model.
Ubiquitous knockdown of Dmel\Prx3 mediated by RNAi (resulting in mRNA expression levels 46% of wild type) fails to impact viability or normal lifespan; however, adult lifespan on medium containing paraquat is reduced. Prx3 knockdown in neurons and glia, but not in muscles, significantly reduces motor behavior in an open-field arena assay.
[updated Jul. 2022 by FlyBase; FBrf0222196]
Autosomal recessive cerebellar ataxias (ARCA) are a heterogeneous group of rare neurological disorders involving both central and peripheral nervous system, and in some case other systems and organs, and characterized by degeneration or abnormal development of cerebellum and spinal cord, autosomal recessive inheritance and, in most cases, early onset occurring before the age of 20 years (Palau and Espinos, 2006; pubmed:17112370).
The hereditary ataxias are a group of genetic disorders characterized by slowly progressive incoordination of gait and often associated with poor coordination of hands, speech, and eye movements. Frequently, atrophy of the cerebellum occurs. [from Gene Reviews, Hereditary Ataxia Overview; pubmed:20301317; 2017.06.16]
See also Jayadev and Bird, 2013 (pubmed:23538602).
Autosomal recessive spinocerebellar ataxia is a neurologic disorder characterized by onset of progressive gait difficulties, eye movement abnormalities, and dysarthria in the first or second decade of life (summary, Dy et al, 2105; pubmed:26224725). [from MIM:609270; 2020.07.13]
[SPINOCEREBELLAR ATAXIA, AUTOSOMAL RECESSIVE 32; SCAR32](https://omim.org/entry/619862)
[PEROXIREDOXIN 3; PRDX3](https://omim.org/entry/604769)
The clinical presentation of individuals with PRDX3 mutations consists of mild-to-moderate progressive cerebellar ataxia with concomitant hyper- and hypokinetic movement disorders, severe early-onset cerebellar atrophy, and in part olivary and brainstem degeneration (FBrf0249324).
Autosomal recessive spinocerebellar ataxia-32 (SCAR32) is a neurologic disorder characterized by the onset of gait ataxia in the second or third decades of life. The disorder is slowly progressive. Other classic features include upper limb ataxia, oculomotor signs, dysphagia, and dysarthria. Some patients may have hyper- or hypokinetic movement abnormalities. Brain imaging shows cerebellar atrophy (Rebelo et al., 2021; pubmed:33889951). [from MIM:619862; 2022.07.20]
PRDX3-related spinocerebellar ataxia exhibits autosomal recessive inheritance (FBrf0249324).
Autosomal recessive spinocerebellar ataxia-32 (SCAR32) is caused by homozygous or compound heterozygous mutation in the PRDX3 gene. [from MIM:619862; 2022.07.20]
PRDX3 encodes a mitochondrial protein with antioxidant function; it plays a role in cell protection against oxidative stress by detoxifying peroxides. [Gene Cards, PRDX3; 2021.07.13]
Patient fibroblasts showed a lack of PRDX3 protein, resulting in decreased glutathione peroxidase activity and decreased mitochondrial maximal respiratory capacity (FBrf0249324).
One to one: 1 human gene to 1 Drosophila gene; multiple related genes in both species.
High-scoring ortholog of human PRDX3 (1 Drosophila to 1 human, multiple related genes in both species). Dmel\Prx3 shares 64% identity and 78% similarity with the human gene.
